Activin family ligands (Activin)

Activins are a group of dimeric growth factors belonging to the transforming growth factor-beta (TGF-beta) superfamily, primarily composed of various combinations of inhibin beta subunits (beta-A, beta-B, beta-C, and beta-E). They were originally identified as regulators of follicle-stimulating hormone (FSH) secretion but are now recognized for their pleiotropic roles in cell proliferation, differentiation, apoptosis, and immune regulation. Activins signal by binding to a heteromeric complex of type II (ACVR2A or ACVR2B) and type I (ALK4 or ALK7) serine/threonine kinase receptors, which subsequently activates the SMAD2/3 intracellular signaling pathway. In pathological states, overproduction of activins, particularly Activin A and Activin B, is associated with cancer cachexia, organ fibrosis, chronic inflammation, and muscle wasting. Therapeutic strategies targeting this family include ligand traps, such as sotatercept and luspatercept, which sequester circulating ligands, and monoclonal antibodies like garetosmab that specifically neutralize individual activin isoforms. These interventions are being explored for conditions ranging from pulmonary arterial hypertension and anemia to sarcopenia and fibrotic diseases.

Other names

Activin AActivin BActivin ABActivin CActivin EInhibin beta subunitsINHBAINHBBINHBCINHBE

Ligand sequestration via soluble receptor fusion proteins (ligand traps) or neutralization via monoclonal antibodies, preventing binding to type II and type I activin receptors and subsequent SMAD2/3 signaling.